Cancer Flashcards
Types of familial CRC (15% of CRC)
3-5% hnpcc,
What does MSI-H indicate in CRC
25% associated with germline MMR mutations but 10-15% sporadic CRC also have. Therefore need to supplement with further test
How is IHC used for CRC diagnosis
Staining looks for loss of MMR gene expression. Ie detects product +/- of MMR genes. Loss of MSH2 stain = absent IHC expression of MSH2 and MSh6, loss of MLH1= absent IHC of mlh1 and pms2. Isolated absence of msh6 or pms2 = mutation in that gene.
What is MS-PCR used for in crc testing
Methylation status of mlh1 promotor . Often seen in sporadic non-lynch CRC and associated with BRAF V600E
Why use BRAF screen in CRC?
Indicate if CRC sporadic before test MMR genes. Common in non-lynch MSI-H tumours.
Discuss EPCAM mutation in lynch
Upstream of msh2. Deletion in EPCAM -> transcriptional read through and silencing of msh2
Mutation seen in most FAP
75% have APC mutation
Example of genotype-phenotype correlations in familial cancer syndromes
APC mutations- ass different types of FAP. Attenuated Fap, Gardner syndrome, diff ages of onset
Techniques to test for APC abnormalities in FAP?
Sequencing detects 90% but mlpa useful to detect 10% with whole APC deletion
Example of presumptions tic test available to minors
Fap
Example of sumilar phenotype-different mechanism in CRC
Fap and map. APC and MutYH
Inheritance pattern of APC
AD
Inheritance pattern of MutYH
AR
What is Her2?
Receptor TK encoded by EBBR2- amplified in 20-30% early stage breast cancer. Ass with more aggressive disease
Side effects of herceptin
Increased risk heart diseas, 15% still relapse
How is her2 amp measured
IHC 0-1: negative, 2: intermediate, 3: high. High will have fish test which measures amount per cell and will be either + or -
How do PARPi work for breast cancer patients
Cause ds breaks to form. As brca positive cancer can’t repair, the cells apoptose
% lung cancer that is nsclc
70%
Which TKI used in nsclc . Which gene mutation is it effective against? Drawback?
Gefitinib. Directed against egfr mutation by blocking arp binding sites. Only works in 10% patients
Importance of detecting kras mutation in nsclc
Mutually exclusive to egfr mutation- in 22% nsclc. Not sensitive to egfr TKI or adjuvent chemo
What causes EML4-ALK fusion in lung adenocarcinoma
Para inv 2p21p23
Drug used for eml4 - alk fusion in lung adenocarcinoma. Disadvantage for nice recommendation
Crizotinib. Nice won’t rec due to cost
Challenges to stratified medicine
Standardisation of testing, linking to patient histories- privacy, large datasets req, need to understand mech not just ID a link, ethnicity role?, epigenetics effects?
Why use stratified medicine
Current drugs only effective in 30-60%, cost reduction, prevent adverse reactions, right drugs at right time, smarter monitoring fits with 5yfv
